Janet Stocks

![Graphic][1] A great sense of loss and sadness marked the recent death of Philip Quanjer, who passed away peacefully at his home in Nijverdal, the Netherlands on July 26, 2017 after a long and courageous battle against cancer, during which he defied all odds in order to complete the tasks he had set himself. Philip was a highly respected member of the global respiratory community, who devoted his life to understanding and describing lung health, remaining highly active in his field up to a few weeks before his death. Indeed, after “retiring” in 1997, he went on to publish a further 90 papers, an astonishing 55 of which being published during the last five years of his life. His efforts since the 1980s to improve the standard of lung function testing and develop more reliable reference values with which to interpret the results of such tests have won him international acclaim and immense respect and admiration from the global respiratory community. Such developments were essential in order to improve early detection of respiratory disease, irrespective of age, sex or ethnic background, and to clarify what factors impact negatively on lung development. Philip was born on September 12, 1936 in Pontianak (Netherlands East Indies, now Indonesia) and spent his formative years in a Japanese concentration camp (where he learnt to swim in crocodile infested rivers!) until liberation in 1945. His first two years of formal education, which did not commence until he was nine years of age, were spent in Thailand and Indonesia before his family returned to the Netherlands in 1948. Philip met the love of his life and future wife, Else Meijerink, while they were both high school students. They married in 1960, while he was still a student at Groningen University medical school (1955–1963), had four children (two sons … [1]: /embed/inline-graphic-1.gif

There is increasing evidence that chronic obstructive pulmonary disease (COPD) is not simply a disease of old age that is largely restricted to heavy smokers, but may be associated with insults to the developing lung during foetal life and the first few years of postnatal life, when lung growth and development are rapid. A better understanding of the long-term effects of early life factors, such as intrauterine growth restriction, prenatal and postnatal exposure to tobacco smoke and other pollutants, preterm delivery and childhood respiratory illnesses, on the subsequent development of chronic respiratory disease is imperative if appropriate preventive and management strategies to reduce the burden of COPD are to be developed. The extent to which insults to the developing lung are associated with increased risk of COPD in later life depends on the underlying cause, timing and severity of such derangements. Suboptimal conditions in utero result in aberrations of lung development such that affected individuals are born with reduced lung function, which tends to remain diminished throughout life, thereby increasing the risk both of wheezing disorders during childhood and subsequent COPD in genetically susceptible individuals. If the current trend towards the ever-increasing incidence of COPD is to be reversed, it is essential to minimize risks to the developing lung by improvements in antenatal and neonatal care, and to reduce prenatal and postnatal exposures to environmental pollutants, including passive tobacco smoke. Furthermore, adult physicians need to recognize that lung disease is potentially associated with early life insults and provide better education regarding diet, exercise and avoidance of smoking to preserve precious reserves of lung function in susceptible adults. This review focuses on factors that adversely influence lung development in utero and during the first 5 years of life, thereby predisposing to subsequent COPD.

Lung disease begins early in life in cystic fibrosis (CF), yet our understanding of CF lung abnormalities in the first years of life remains limited. By facilitating earlier diagnosis, newborn screening for CF provides the opportunity to understand and characterize presymptomatic lung disease in infants and young children. This could lead to earlier interventions to mitigate disease progression at a time when therapeutic intervention or prevention may be most effective. This article reviews lung function tests that can be used during the first 5 years of life and discusses their potential applications as objective outcomes for clinical monitoring or research. During the past decade, commercial equipment for assessing a wide range of lung function tests in infants and preschool children has become available together with international guidelines and improved reference equations with which to interpret results. The lung clearance index, derived from multiple breath washout, has been shown to be far more sensitive to early CF lung disease than conventional spirometric assessments. Although limited evidence exists as to whether incorporating lung function tests into routine clinical care can improve patient outcomes during the early years, this is likely to be helpful in preschool children if more sensitive tests such as the multiple breath washout become more widely available. There is an urgent need to assess which infant and preschool lung function outcomes will provide the most robust outcome measures in collaborative multicenter studies, so that they can be incorporated into early therapeutic intervention studies.

Rationale: With increasing use of infant pulmonary function tests (IPFTs) in both clinical and research studies, appropriate interpretation of results is essential.Objectives: To investigate the potential bias associated with “normalising” IPF by expressing results as a ratio of body size and to develop reference ranges for tidal breathing parameters, passive respiratory mechanics (compliance [C_rs] and resistance [R_rs]) and plethysmographic functional residual capacity (FRC_p) for white infants during the first 2 years of life.Methods: IPFTs were measured using the Jaeger BabyBody system and standardized protocols. Reference equations, adjusted for body size, age, and sex where appropriate, were created using multilevel modeling.Results: The ratio of lung function to body length changes markedly with growth, thereby precluding its use for any outcome. While the ratio of tidal volume and C_rs to body weight remained relatively constant with growth, this was not the case for FRC_p. Even in healthy infants, a strong inverse relationship was observed between lung function/body weight and weight z‐score which could distort interpretation of results in growth‐restricted infants with lung disease, such as cystic fibrosis. Reference equations were derived from 153 healthy white infants on 232 test occasions (median age 35.5 weeks [range: 2.6–104.7]). Crown‐heel length was the strongest predictor of IPF.Conclusions: When reporting IPF, use of size‐corrected ratios should be discouraged, with interpretation instead based on appropriate reference equations. The current equations are applicable to white infants and young children up to 2 years of age, studied using the same commercially available equipment. The extent to which these equations are applicable to infants and young children of other ethnic backgrounds or who are tested with different equipment needs to be established. Pediatr Pulmonol. 2013; 48:370–380.

Background Long-term benefits of newborn screening (NBS) for cystic fibrosis (CF) have been established with respect to nutritional status, but effects on pulmonary health remain unclear. Hypothesis With early diagnosis and commencement of standardised treatment, lung function at ∼3 months of age is normal in NBS infants with CF. Methods Lung clearance index (LCI) and functional residual capacity (FRC) using multiple breath washout (MBW), plethysmographic (pleth) FRC and forced expirations from raised lung volumes were measured in 71 infants with CF (participants in the London CF Collaboration) and 54 contemporaneous healthy controls age ∼3 months. Results Compared with controls, and after adjustment for body size and age, LCI, FRC_MBW and FRC_pleth were significantly higher in infants with CF (mean difference (95% CI): 0.5 (0.1 to 0.9), p=0.02; 0.4 (0.1 to 0.7), p=0.02 and 0.9 (0.4 to 1.3), p0.5) and flows (FEF_25–75) were significantly lower (−0.9 (−1.3 to −0.6), p1.96 z-scores) and 25% (17/68) an abnormally low FEV_0.5 (below −1.96 z-scores). While only eight infants with CF had abnormalities of LCI and FEV_0.5, using both techniques identified abnormalities in 35% (24/68). Hyperinflation (FRC_pleth >1.96 z-scores) was identified in 18% (10/56) of infants with CF and was significantly correlated with diminished FEF_25–75 (r=−0.43, p0.5. Conclusion Despite early diagnosis of CF by NBS and protocol-driven treatment in specialist centres, abnormal lung function, with increased ventilation inhomogeneity and hyperinflation and diminished airway function, is evident in many infants with CF diagnosed through NBS by 3 months of age.